Constructing and Validating 3D-pharmacophore Models to a Set of MMP-9 Inhibitors for Designing Novel Anti-melanoma Agents
Turra KM; Rivelli DP; Barros SBD; de Souza, Ana Olívia.
Mol. Inf
; 35(6-7): p. 238-252, 2016.
Artículo
| SES-SP, SESSP-IBPROD, SES-SP | ID: but-ib13653
A receptor-independent (RI) four-dimensional structure-activity relationship (4D-QSAR) formalism was applied to a set of sixty-four -N-biaryl ether sulfonamide hydroxamate derivatives, previously reported as potent inhibitors against matrix metalloproteinase subtype 9 (MMP-9). MMP-9 belongs to a group of enzymes related to the cleavage of several extracellular matrix components and has been associated to cancer invasiveness/metastasis. The best RI 4D-QSAR model was statistically significant (N=47; r(2)=0.91; q(2)=0.83; LSE=0.09; LOF=0.35; outliers=0). Leave-N-out (LNO) and y-randomization approaches indicated the QSAR model was robust and presented no chance correlation, respectively. Furthermore, it also had good external predictability (82%) regarding the test set (N=17). In addition, the grid cell occupancy descriptors (GCOD) of the predicted bioactive conformation for the most potent inhibitor were successfully interpreted when docked into the MMP-9 active site. The 3D-pharmacophore findings were used to predict novel ligands and exploit the MMP-9 calculated binding affinity through molecular docking procedure
Biblioteca responsable:
BR78.1
Ubicación: BR78.1
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